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Friday, Jan 09, 2009 | 12:42 PM
Madisons Foundation - Moms And Dads In Search Of Needed Support
Agammaglobulinemia, X-linked (XLA)
Bruton's Agammaglobulinemia
Wednesday, 16 July 2003
Last Updated Wednesday, 03 August 2005
What
X-linked agammaglobulinemia (XLA) is a disease of the immune system that presents in early childhood. There are many cells that work as part of the body’s immune system to help fight infection. One type of cell is the B lymphocyte which plays a part in producing a protein called immunoglobulins or antibodies. There are five major classes of immunoglobulins, and IgG (also called gamma globulin) is one of these classes. Children with XLA have low or absent levels of immunoglobulins, including IgG, so they have an extremely difficult time fighting off infections. Certain bacteria, especially Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Pseudomonas are common causes of infection in XLA.Who
XLA affects approximately 1 in 250,000 people of all races and ethnicities. Almost all cases are male patients due to the inheritance pattern of this disease. This disorder is X-linked, meaning the abnormal gene is passed on through the X chromosome that determines gender. Females inherit two X chromosomes, and when they inherit a defective X chromosome, they have one normal X chromosome which overrides the defective gene expression on the affected X chromosome. Males, however, inherit one X chromosome from the mother and one Y chromosome from the father. When the X chromosome is defective, boys do not have another normal X chromosome to counterbalance the genetic effect and so will have XLA. Approximately two thirds of people with XLA have inherited the abnormal gene from a parent, while one third get the disease from a new and sporadic mutation.Signs and Symptoms
Children with XLA will have low or absent levels of immunoglobulins and present with severe infections. These infections usually begin between the ages of 6 months to 18 months, but can occur earlier or later than this common age range. The infections do not start until then because babies receive some maternal immunoglobulin while in the womb and are usually protected from the bacteria listed above for 6 to 18 months after birth. The exact age of onset and the severity of symptoms involved will vary with each individual. The most common symptom is recurrent or severe bacterial infections of the respiratory tract, for example: sinusitis, otitis (ear infections), or pneumonia. Another common symptom is severe and persistent diarrhea due to infection of the gastrointestinal tract. Children with XLA can also develop infections of the skin, eye and blood (sepsis). Most children with XLA will have small or absent tonsils, adenoids, and lymph nodes. Some may have arthritis of the knees, ankles, and other large joints with swelling and limited range of motion. Some may also have slow growth. Children with XLA may have an increased risk for tumors, but this is not conclusive and research is still ongoing. Despite the lack of immunoglobulins in XLA, other parts of the immune system should still function properly. These children should have normally functioning T lymphocytes so the body will be able to normally react to most viruses (including chickenpox) and the tuberculosis bacterium.Possible Causes
In X-linked agammaglobulinemia there is an abnormal gene (the B cell tyrosine kinase gene, Btk) on the X chromosome. This gene has DNA that tells the body to make specific proteins that are involved with the proper functioning and growth of B cells. Because this gene is abnormal, the B cells cannot develop and produce immunoglobulins to fight off certain bacterial infections.Diagnosis
The diagnosis is made by getting a history of serious infections and obtaining blood tests showing low levels of IgG in comparison to the expected normal amount for the child’s age. The other immunoglobulins, including IgA, IgM and IgE, are also low or undetectable. There are other diseases that cause low immunoglobulins in children, and these must be excluded because they are often treated differently. In XLA, there will also be low amounts of B lymphocytes circulating in the blood. To definitively diagnose XLA in a child, the child’s X chromosome can be studied to determine if the abnormal Btk gene is present. Tests, such as the Western Blot and flow cytometry tests, can be done to detect this pattern that will suggest XLA. Imaging studies, such as head radiographs and neck CT scans, may be done to determine the absence of tonsils and adenoids.Treatment
It is important to diagnose and treat children with XLA early to avoid permanent structural damage of the lungs from the recurrent infections. A child with XLA will need to receive IgG about once each month for his/her entire life. The IgG is usually given to the child as an intravenous infusion (called IVIG) which helps to reduce the severity and frequency of respiratory and gastrointestinal infections. Any infection in the child should be treated immediately and aggressively with antibiotics that are appropriate for the specific organism causing the infection. One of the most serious concerns for children with XLA is lung damage due to the recurrent lung infections. Therefore, bronchodilators, steroid inhalers and pulmonary function tests may be required to test lung function and to ensure proper lung functioning. Lotions and topical steroids may be used to control skin infections. If the infection is very severe and cannot be controlled at home, the child may need temporary hospitalization for intravenous antibiotics. Children with XLA should follow a normal diet supplemented by a multivitamin. Children with XLA should not receive any live viral vaccines (ie, oral polio, measles and chickenpox) because the body cannot form a proper immune response against the small amount of virus in the vaccine and they may get that infection. Although there is currently no cure for XLA, research is being done on gene therapy as a possible way to cure this disease.Prognosis
It is important to diagnose XLA and begin treatment early, preferably before 5 years of age. If this is done, normal growth and development is expected. Children with XLA should be closely followed by their pediatrician and an immunologist throughout life to monitor lung function and possible development of malignancy. Thus, with regular monthly IVIG, appropriate treatment for infections, and careful monitoring for lung damage, most individuals with XLA can expect to lead relatively normal lives through adulthood.Connect with other parents
In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.Weblinks
National Primary Immunodeficiency Resource Center
This is a website with good information about XLA and links to ongoing research.
Health A to Z
This website has a well-written summary of the disease with definitions of key terms.
Medline Plus
This website has a good description of the disease and tests involved for diagnosis.